Mesh rolled scaffold and advanced bioreactor

Abstract

The present invention provides mesh rolled scaffold devices and bioreactor systems that can provide a large surface-to-volume ratio for expanded cell culture. The mesh rolled scaffolds minimize shear stress on cultured cells and support sufficient and uniform mass transfer rates of gases and nutrients. The mesh rolled scaffolds can be connected to a media source via holders in bioreactor systems to support large-scale expansion and maintenance of cell cultures. The present invention also provides the bioreactor systems that can include dialyzers and heat exchangers to modify media and other fluids passing through the systems. The bioreactor systems include media and other fluid reservoirs that can support high stirring rates between about 100 and 10000 rpm, and the overall systems can be pressurized between about 1 and 10 atm to increase gas exchange rates.

1 - 15 . (canceled) 
     
     
         16 . A bioreactor system, comprising:
 a rolled scaffold;   at least one cylindrical holder, each comprising a hollow casing sized to fit a rolled scaffold, at least one inlet port at a first end, and at least one outlet port at an opposite second end;   at least one reservoir;   tubing fluidically connecting the at least one reservoir to each of the cylindrical holders; and   at least one pump connected to the tubing.   
     
     
         17 . The bioreactor system of  claim 16 , wherein the rolled scaffold is constructed from at least one substantially planar film and at least one mesh netting rolled into a cylindrical rolled scaffold having alternating layers of film and mesh netting. 
     
     
         18 . The bioreactor system of  claim 16 , wherein the rolled scaffold is constructed from at least one substantially planar film, at least one mesh netting, and at least one adhesion layer rolled into a cylindrical rolled scaffold having alternating layers of film, mesh netting, and adhesion layers. 
     
     
         19 . The bioreactor system of  claim 16 , wherein the rolled scaffold is constructed from at least one substantially planar film having a plurality of elongate spacers attached to the film rolled into a cylindrical rolled scaffold, such that the spacers maintain a space between the rolled film layers. 
     
     
         20 . The bioreactor system of  claim 16 , wherein the at least one reservoir is fluidically connected to one or more media sources, gas sources, chemical reagents, and combinations thereof. 
     
     
         21 . The bioreactor system of  claim 16 , wherein the tubing comprises one or more access ports upstream from the cylindrical holders, downstream from the cylindrical holders, or both. 
     
     
         22 . The bioreactor system of  claim 16 , wherein the tubing comprises one or more sensors upstream from the cylindrical holders, downstream from the cylindrical holders, or both. 
     
     
         23 . The bioreactor system of  claim 21 , wherein the one or more sensors are selected from the group consisting of: temperature sensors, flow sensors, pH sensors, gas concentration sensors, glucose sensors, and analyte sensors. 
     
     
         24 . The bioreactor system of  claim 16 , wherein the tubing comprises one or more stopcocks or valves configured to stop or divert flow of fluid within the system. 
     
     
         25 . The bioreactor system of  claim 16 , wherein the rolled scaffold, each within a cylindrical holder, is connected to the at least one reservoir in series, in parallel, and combinations thereof. 
     
     
         26 . The bioreactor system of  claim 16 , wherein the tubing further comprises a dialyzer configured to separate out components of fluid within the tubing and to introduce components into fluid within the tubing. 
     
     
         27 . The bioreactor system of  claim 16 , wherein the tubing further comprises at least one heat exchanger configured to change the temperature of fluid within the tubing, such that the at least one reservoir is maintained at a temperature that is different from the temperature of the rolled scaffold. 
     
     
         28 . The bioreactor system of  claim 26 , wherein the at least one heat exchanger is positioned upstream from the rolled scaffold, downstream from the rolled scaffold, or both. 
     
     
         29 . The bioreactor system of  claim 16 , wherein the at least one reservoir comprises a stirring impeller configured to rotate between 100 and 10000 rpm. 
     
     
         30 . The bioreactor system of  claim 16 , wherein the system is pressurized between 1 atm and 10 atm. 
     
     
         31 . The bioreactor system of  claim 16 , wherein the tubing further comprises at least one dialyzer and at least one heat exchanger.